CD4(+) T follicular helper (TFH) cells are central for generation of long-term B-cell immunity. A defining phenotypic attribute of TFH cells is the expression of the chemokine R CXCR5, and TFH cells are typically identified by co-expression of CXCR5 together with other markers such as PD-1, ICOS, and Bcl-6. Herein, we report high-level expression of the nutrient transporter folate R 4 (FR4) on TFH cells in acute viral infection. Distinct from the expression profile of conventional TFH markers, FR4 was highly expressed by naive CD4(+) T cells, was downregulated after activation and subsequently re-expressed on TFH cells. Furthermore, FR4 expression was maintained, albeit at lower levels, on memory TFH cells. Comparative gene expression profiling of FR4(hi) versus FR4(lo) Ag-specific CD4(+) effector T cells revealed a molecular signature consistent with TFH and TH1 subsets, respectively. Interestingly, genes involved in the purine metabolic pathway, including the ecto-enzyme CD73, were enriched in TFH cells compared with TH1 cells, and phenotypic analysis confirmed expression of CD73 on TFH cells. As there is now considerable interest in developing vaccines that would induce optimal TFH cell responses, the identification of two novel cell surface markers should be useful in characterization and identification of TFH cells following vaccination and infection.

中文翻译：

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鉴定小鼠 CD4(+) T 滤泡辅助细胞的新标记。

CD4(+) T 滤泡辅助 (TFH) 细胞是产生长期 B 细胞免疫的核心。TFH 细胞的一个决定性表型属性是趋化因子 R CXCR5 的表达，而 TFH 细胞通常通过 CXCR5 与其他标记物（如 PD-1、ICOS 和 Bcl-6）的共表达来识别。在此，我们报告了急性病毒感染中 TFH 细胞上营养转运蛋白叶酸 R 4 (FR4) 的高水平表达。与常规 TFH 标记的表达谱不同，FR4 由幼稚 CD4(+) T 细胞高度表达，激活后下调，随后在 TFH 细胞上重新表达。此外，FR4 表达在记忆 TFH 细胞上保持不变，尽管水平较低。FR4(hi) 与 FR4(lo) Ag 特异性 CD4(+) 效应 T 细胞的比较基因表达谱揭示了分别与 TFH 和 TH1 子集一致的分子特征。有趣的是，与 TH1 细胞相比，参与嘌呤代谢途径的基因，包括外酶 CD73，在 TFH 细胞中富集，表型分析证实了 CD73 在 TFH 细胞上的表达。由于现在人们对开发可诱导最佳 TFH 细胞反应的疫苗有相当大的兴趣，因此两种新型细胞表面标记的鉴定应该有助于在接种和感染后表征和鉴定 TFH 细胞。和表型分析证实了 CD73 在 TFH 细胞上的表达。由于现在人们对开发可诱导最佳 TFH 细胞反应的疫苗有相当大的兴趣，因此两种新型细胞表面标记的鉴定应该有助于在接种和感染后表征和鉴定 TFH 细胞。和表型分析证实了 CD73 在 TFH 细胞上的表达。由于现在人们对开发可诱导最佳 TFH 细胞反应的疫苗有相当大的兴趣，因此两种新型细胞表面标记的鉴定应该有助于在接种和感染后表征和鉴定 TFH 细胞。